Selenoproteins of African trypanosomes are dispensable for parasite survival in a mammalian host.

Dublin Core

Título

Selenoproteins of African trypanosomes are dispensable for parasite survival in a mammalian host.

Tema

SELENIO

PROTEINAS

SELENIOCISTEINA

TRIPANOSOMAS

BIBLIOGRAFIA NACIONAL QUIMICA

2016

Abstract

The trace element selenium is found in polypeptides as selenocysteine, the 21stamino acid that is co-translationally inserted into proteins at a UGA codon. In proteins, selenocysteine usually plays a role asan efficient redox catalyst. Trypanosomatids previously examined harbor a full set of genes encodingthe machinery needed for selenocysteine biosynthesis and incorporation into three selenoproteins: SelK,SelT and, the parasite-specific, Seltryp. We investigated the selenoproteome of kinetoplastid speciesin recently sequenced genomes and assessed the in vivo relevance of selenoproteins for African try-panosomes. Database mining revealed that SelK, SelT and Seltryp genes are present in most kinetoplastids,including the free-living species Bodo saltans, and Seltryp was lost in the subgenus Viannia from theNew World Leishmania. Homology and sinteny with bacterial sulfur dioxygenases and sulfur transferasessuggest a putative role for Seltryp in sulfur metabolism. A Trypanosoma brucei selenocysteine synthase(SepSecS) null-mutant, in which selenoprotein synthesis is abolished, displayed similar sensitivity tooxidative stress induced by a short-term exposure to high concentrations of methylglyoxal or H2O2tothat of the parental wild-type cell line. Importantly, the infectivity of the SepSecS knockout cell line wasnot impaired when tested in a mouse infection model and compensatory effects via up-regulation ofproteins involved in thiol-redox metabolism were not observed. Collectively, our data show that seleno-proteins are not required for survival of African trypanosomes in a mammalian host and exclude a rolefor selenoproteins in parasite antioxidant defense and/or virulence. On this basis, selenoproteins can bedisregarded as drug target candidates.